RSUME inhibits VHL and regulates its tumor suppressor function

Oncogene

Volumn 34, Issue 37, 2015, Pages 4855-4866

  Gerez, J ^a,b   Tedesco, L ^a   Bonfiglio, J J ^a,b   Fuertes, M ^a   Barontini, M ^c   Silberstein, S ^a,b   Wu, Y ^d   Renner, U ^d   Paez Pereda M ^d   Holsboer, F ^d   Stalla, G K ^d   Arzt, E ^a,b  

^a Instituto de Investigación en Biomedicina de Buenos Aires   (Argentina)

^b UNIVERSIDAD DE BUENOS AIRES   (Argentina)

^c HOSPITAL DE NIÑOS RICARDO GUTIÉRREZ   (Argentina)

^d MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CULLIN; ELONGIN; HYPOXIA INDUCIBLE FACTOR 1; HYPOXIA INDUCIBLE FACTOR 2ALPHA; RWD DOMAIN CONTAINING PROTEIN SUMO ENHANCER PROTEIN; SUMO PROTEIN; UNCLASSIFIED DRUG; VASCULOTROPIN A; VON HIPPEL LINDAU PROTEIN; RSUME PROTEIN, HUMAN; TRANSCRIPTION FACTOR; VHL PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASSAY; CANCER INHIBITION; CLEAR CELL CARCINOMA; CONTROLLED STUDY; GENE MUTATION; GENE OVEREXPRESSION; GENE SILENCING; HEMANGIOBLASTOMA; HUMAN; HUMAN TISSUE; KIDNEY CARCINOMA; MALE; MOUSE; MUTANT; NONHUMAN; PHEOCHROMOCYTOMA; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; TUMOR GROWTH; TUMOR VASCULARIZATION; UBIQUITINATION; XENOGRAFT; ADRENAL TUMOR; ANIMAL; CEREBELLUM TUMOR; CHLOROCEBUS AETHIOPS; COS 1 CELL LINE; DISEASE COURSE; DOWN REGULATION; GENE EXPRESSION REGULATION; GENETICS; NUDE MOUSE; PATHOLOGY; PHYSIOLOGY; TUMOR CELL CULTURE; TUMOR SUPPRESSOR GENE;

ADRENAL GLAND NEOPLASMS; ANIMALS; CERCOPITHECUS AETHIOPS; CEREBELLAR NEOPLASMS; COS CELLS; DISEASE PROGRESSION; DOWN-REGULATION; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, TUMOR SUPPRESSOR; HEMANGIOBLASTOMA; HUMANS; MALE; MICE; MICE, NUDE; PHEOCHROMOCYTOMA; TRANSCRIPTION FACTORS; TUMOR CELLS, CULTURED; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 84941314198     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2014.407     Document Type: Article

References (73)

1. Carbia-Nagashima A, Gerez J, Perez-Castro C, Paez-Pereda M, Silberstein S, Stalla GK et al. RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell 2007; 131: 309-323.
2. Geiss-Friedlander R, Melchior F. Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol 2007; 8: 947-956.
3. Hay RT. SUMO: a history of modification. Mol Cell 2005; 18: 1-12.
4. Druker J, Liberman AC, Antunica-Noguerol M, Gerez J, Paez-Pereda M, Rein T et al. RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity. Mol Cell Biol 2013; 33: 2116-2127.
5. Gerez J, Fuertes M, Tedesco L, Silberstein S, Sevlever G, Paez-Pereda M et al. In silico structural and functional characterization of the RSUME splice variants. PLoS One 2013; 8: e57795.
6. Huang CC, Tu SH, Lien HH, Jeng JY, Huang CS, Huang CJ et al. Concurrent gene signatures for han chinese breast cancers. PLoS ONE 2013; 8: e76421.
7. Schneider BP, Li L, Miller K, Flockhart D, Radovich M, Hancock BA et al. Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103. J Clin Oncol 2011; 29: Supplementary Abstract 1000.
8. Bergmann TK, Vach W, Feddersen S, Eckhoff L, Green H, Herrstedt J et al. GWASbased association between RWDD3 and TECTA variants and paclitaxel induced neuropathy could not be confirmed in Scandinavian ovarian cancer patients. Acta Oncol 2013; 52: 871-874.
9. Rojewska E, Korostynski M, Przewlocki R, Przewlocka B, Mika J. Expression profiling of genes modulated by minocycline in a rat model of neuropathic pain. Mol Pain 2014; 10: 47.
10. Willi-Monnerat S, Migliavacca E, Surdez D, Delorenzi M, Luthi-Carter R, Terskikh AV. Comprehensive spatiotemporal transcriptomic analyses of the ganglionic eminences demonstrate the uniqueness of its caudal subdivision. Mol Cell Neurosci 2008; 37: 845-856.
11. Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 1999; 15: 551-578.
12. Brahimi-Horn MC, Pouyssegur J. HIF at a glance. J Cell Sci 2009; 122: 1055-1057.
13. Kaelin WG Jr., Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 2008; 30: 393-402.
14. Keith B, Johnson RS, Simon MC. HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 2012; 12: 9-22.
15. Pugh CW, O'Rourke JF, Nagao M, Gleadle JM, Ratcliffe PJ. Activation of hypoxiainducible factor-1; definition of regulatory domains within the alpha subunit. J Biol Chem 1997; 272: 11205-11214.
16. Berra E, Pouyssegur J. The silencing approach of the hypoxia-signaling pathway. Methods Enzymol 2007; 435: 107-121.
17. Greer SN, Metcalf JL, Wang Y, Ohh M. The updated biology of hypoxiainducible factor. EMBO J 2012; 31: 2448-2460.
18. Kaelin WG Jr. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002; 2: 673-682.
19. Yu F, White SB, Zhao Q, Lee FS. HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc Natl Acad Sci USA 2001; 98: 9630-9635.
20. Schwartz AL, Ciechanover A. Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu Rev Pharmacol Toxicol 2009; 49: 73-96.
21. Semenza GL. Oxygen sensing, homeostasis, and disease. N Engl J Med 2011; 365: 537-547.
22. Nunez-O'Mara A, Berra E. Deciphering the emerging role of SUMO conjugation in the hypoxia-signaling cascade. Biol Chem 2013; 394: 459-469.
23. Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol 2004; 22: 4991-5004.
24. Maher ER, Kaelin WG Jr. von Hippel-Lindau disease. Medicine (Baltimore) 1997; 76: 381-391.
25. Keefe SM, Nathanson KL, Rathmell WK. The molecular biology of renal cell carcinoma. Semin Oncol 2013; 40: 421-428.
26. Jonasch E, Futreal PA, Davis IJ, Bailey ST, Kim WY, Brugarolas J et al. State of the science: an update on renal cell carcinoma. Mol Cancer Res 2012; 10: 859-880.
27. Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE et al. Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2000; 2: 423-427.
28. Kaelin WG Jr. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer 2008; 8: 865-873.
29. Bae SH, Jeong JW, Park JA, Kim SH, Bae MK, Choi SJ et al. Sumoylation increases HIF-1alpha stability and its transcriptional activity. Biochem Biophys Res Commun 2004; 324: 394-400.
30. Cheng J, Kang X, Zhang S, Yeh ET. SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell 2007; 131: 584-595.
31. Kim WY, Safran M, Buckley MR, Ebert BL, Glickman J, Bosenberg M et al. Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J 2006; 25: 4650-4662.
32. Cai Q, Verma SC, Kumar P, Ma M, Robertson ES. Hypoxia inactivates the VHL tumor suppressor through PIASy-mediated SUMO modification. PLoS ONE 2010; 5: e9720.
33. Chien W, Lee KL, Ding LW, Wuensche P, Kato H, Doan NB et al. PIAS4 is an activator of hypoxia signalling via VHL suppression during growth of pancreatic cancer cells. Br J Cancer 2013; 109: 1795-1804.
34. Rathmell WK, Hickey MM, Bezman NA, Chmielecki CA, Carraway NC, Simon MC. In vitro and in vivo models analyzing von Hippel-Lindau disease-specific mutations. Cancer Res 2004; 64: 8595-8603.
35. Rechsteiner MP, von Teichman A, Nowicka A, Sulser T, Schraml P, Moch H. VHL gene mutations and their effects on hypoxia inducible factor HIFalpha: identification of potential driver and passenger mutations. Cancer Res 2011; 71: 5500-5511.
36. Hacker KE, Lee CM, Rathmell WK.. VHL type 2B mutations retain VBC complex form and function. PLoS ONE 2008; 3: e3801.
37. Skuli N, Majmundar AJ, Krock BL, Mesquita RC, Mathew LK, Quinn ZL et al. Endothelial HIF-2alpha regulates murine pathological angiogenesis and revascularization processes. J Clin Invest 2012; 122: 1427-1443.
38. Kang X, Li J, Zou Y, Yi J, Zhang H, Cao M et al. PIASy stimulates HIF1alpha SUMOylation and negatively regulates HIF1alpha activity in response to hypoxia. Oncogene 2010; 29: 5568-5578.
39. van Hagen M, Overmeer RM, Abolvardi SS, Vertegaal AC. RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated Hypoxia-Inducible Factor-2alpha. Nucleic Acids Res 2010; 38: 1922-1931.
40. Cimarosti H, Lindberg C, Bomholt SF, Ronn LC, Henley JM. Increased protein SUMOylation following focal cerebral ischemia. Neuropharmacology 2008; 54: 280-289.
41. Yang W, Sheng H, Warner DS, Paschen W. Transient focal cerebral ischemia induces a dramatic activation of small ubiquitin-like modifier conjugation. J Cereb Blood Flow Metab 2008; 28: 892-896.
42. Huang C, Han Y, Wang Y, Sun X, Yan S, Yeh ET et al. SENP3 is responsible for HIF-1 transactivation under mild oxidative stress via p300 de-SUMOylation. EMBO J 2009; 28: 2748-2762.
43. Shan B, Gerez J, Haedo M, Fuertes M, Theodoropoulou M, Buchfelder M et al. RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells. Endocr Relat Cancer 2012; 19: 13-27.
44. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012; 2: 401-404.
45. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013; 6: pl1.
46. Cancer Genome Atlas Research Network, Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 2013; 499: 43-49.
47. Hoffman MA, Ohh M, Yang H, Klco JM, Ivan M, Kaelin WG Jr. von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF. Hum Mol Genet 2001; 10: 1019-1027.
48. Knauth K, Bex C, Jemth P, Buchberger A. Renal cell carcinoma risk in type 2 von Hippel-Lindau disease correlates with defects in pVHL stability and HIF-1alpha interactions. Oncogene 2006; 25: 370-377.
49. Semenza GL. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 2013; 123: 3664-3671.
50. Knauth K, Cartwright E, Freund S, Bycroft M, Buchberger A. VHL mutations linked to type 2C von Hippel-Lindau disease cause extensive structural perturbations in pVHL. J Biol Chem 2009; 284: 10514-10522.
51. Rathmell WK, Godley PA. Recent updates in renal cell carcinoma. Curr Opin Oncol 2010; 22: 250-256.
52. Cowey CL, Rathmell WK. VHL gene mutations in renal cell carcinoma: role as a biomarker of disease outcome and drug efficacy. Curr Oncol Rep 2009; 11: 94-101.
53. Brooks SA, Brannon AR, Parker JS, Fisher JC, Sen O, Kattan MW et al. ClearCode34: A prognostic risk predictor for localized clear cell renal cell carcinoma. Eur Urol 2014; 66: 77-84.
54. Gnarra JR, Zhou S, Merrill MJ, Wagner JR, Krumm A, Papavassiliou E et al. Posttranscriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc Natl Acad Sci USA 1996; 93: 10589-10594.
55. Iliopoulos O, Kibel A, Gray S, Kaelin WG Jr. Tumour suppression by the human von Hippel-Lindau gene product. Nat Med 1995; 1: 822-826.
56. Zimmer M, Doucette D, Siddiqui N, Iliopoulos O. Inhibition of hypoxia-inducible factor is sufficient for growth suppression of VHL-/-tumors. Mol Cancer Res 2004; 2: 89-95.
57. Maranchie JK, Vasselli JR, Riss J, Bonifacino JS, Linehan WM, Klausner RD. The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell 2002; 1: 247-255.
58. Richard DE, Berra E, Pouyssegur J. Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells. J Biol Chem 2000; 275: 26765-26771.
59. Tanos T, Marinissen MJ, Leskow FC, Hochbaum D, Martinetto H, Gutkind JS et al. Phosphorylation of c-Fos by members of the p38 MAPK family. Role in the AP-1 response to UV light. J Biol Chem 2005; 280: 18842-18852.
60. Groulx I, Lee S. Oxygen-dependent ubiquitination and degradation of hypoxiainducible factor requires nuclear-cytoplasmic trafficking of the von Hippel-Lindau tumor suppressor protein. Mol Cell Biol 2002; 22: 5319-5336.
61. Safran M, Kim WY, O'Connell F, Flippin L, Gunzler V, Horner JW et al. Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production. Proc Natl Acad Sci USA 2006; 103: 105-110.
62. Kondo K, Klco J, Nakamura E, Lechpammer M, Kaelin WG Jr. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 2002; 1: 237-246.
63. Post DE, Van Meir EG. Generation of bidirectional hypoxia/HIF-responsive expression vectors to target gene expression to hypoxic cells. Gene Ther 2001; 8: 1801-1807.
64. Schoenfeld AR, Davidowitz EJ, Burk RD. Elongin BC complex prevents degradation of von Hippel-Lindau tumor suppressor gene products. Proc Natl Acad Sci USA 2000; 97: 8507-8512.
65. Desterro JM, Rodriguez MS, Hay RT. SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation. Mol Cell 1998; 2: 233-239.
66. Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH et al. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem 2001; 276: 35368-35374.
67. Rodriguez MS, Dargemont C, Hay RT. SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting. J Biol Chem 2001; 276: 12654-12659.
68. Juengel E, Engler J, Natsheh I, Jones J, Mickuckyte A, Hudak L et al. Combining the receptor tyrosine kinase inhibitor AEE788 and the mammalian target of rapamycin (mTOR) inhibitor RAD001 strongly inhibits adhesion and growth of renal cell carcinoma cells. BMC Cancer 2009; 9: 161.
69. Lolkema MP, Gervais ML, Snijckers CM, Hill RP, Giles RH, Voest EE et al. Tumor suppression by the von Hippel-Lindau protein requires phosphorylation of the acidic domain. J Biol Chem 2005; 280: 22205-22211.
70. Castro CP, Giacomini D, Nagashima AC, Onofri C, Graciarena M, Kobayashi K et al. Reduced expression of the cytokine transducer gp130 inhibits hormone secretion, cell growth, and tumor development of pituitary lactosomatotrophic GH3 cells. Endocrinology 2003; 144: 693-700.
71. Paez-Pereda M, Giacomini D, Refojo D, Nagashima AC, Hopfner U, Grubler Y et al. Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk. Proc Natl Acad Sci USA 2003; 100: 1034-1039.
72. Huang J, Zhao Q, Mooney SM, Lee FS. Sequence determinants in hypoxiainducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3. J Biol Chem 2002; 277: 39792-39800.
73. Cockman ME, Masson N, Mole DR, Jaakkola P, Chang GW, Clifford SC et al. Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J Biol Chem 2000; 275: 25733-25741.